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Melzi, R.* ; Maffi, P.* ; Nano, R.* ; Sordi, V.* ; Mercalli, A.* ; Scavini, M.* ; Secchi, A.* ; Bonifacio, E.* ; Piemonti, L.*

Rapamycin does not adversely affect intrahepatic islet engraftment in mice and improves early islet engraftment in humans.

Islets 1, 42-49 (2009)
DOI Order publishers version
Open Access Green as soon as Postprint is submitted to ZB.
OBJECTIVE: In this study we examined the effect of rapamycin (RAPA), a key component of the immunosuppressive regimen in clinical islet transplantation, on islet engraftment and function in vivo. METHODS AND RESULTS: Diabetic C57BL/6 or BALB/C recipient mice were transplanted with 350 syngeneic islets through the portal vein (PV-Tx; C57BL/6 n = 60; BALB/C n = 22) and treated with once-daily oral RAPA (1 mg/kg) or vehicle. No differences in post-transplant blood glucose concentrations and glucose tolerance were observed between RAPA- and vehicle-treated mice. The impact of RAPA on human islet engraftment was assessed in 10 patients with type 1 diabetes treated with : 0.1 mg/kg/day rapamycin before islet transplantation. Compared to non pre-treated islet transplant recipients (n = 12), RAPA pre-treated patients had increased blood RAPA concentrations (p = 0.006) and fasting C-peptide concentrations (p = 0.005) in the two weeks post-transplant. RAPA pre-treatment was associated with a reduction in chemokines CCL2 and CCL3 concentrations pre-transplant (p < 0.01), and a dampened chemokine response (p = 0.005) post-transplant. Concordantly, in vitro RAPA inhibited the secretion of CCL2 and CCL3 by monocytes. CONCLUSION: Rapamycin does not adversely affect intrahepatic islet engraftment in the mouse, and potentially improves islet engraftment in humans by an anti-inflammatory mechanism.
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Publication type Article: Journal article
Document type Scientific Article
Reviewing status
Institute(s) Institute for Pancreatic Beta Cell Research (IPI)